This invention relates to treating and/or preventing allergic and inflammatory conditions in a human by administering an amount of desloratadine for a time sufficient to produce a steady state mean plasma concentration of desloratadine to a human in need of such treating.
Loratadine is disclosed in U.S. Pat. No. 4,282,233 as a non-sedating antihistamine useful for treating allergic reactions in animals including humans. See also Claritin brand of Loratadine. Product Information Sheet, dated Jan 1999.Desloratadine is disclosed in U.S. Pat. No. 4,659,716 as a non-sedating antihistamine. The active metabolite of desloratadine, 3-hydroxydesloratadine, is disclosed in U.S. Pat. No. 4,804,666.
For clinical development of desloratadine, it was necessary to characterize the pharmacokinetics of desloratadine and its metabolites to determine the dose required to provide the appropriate concentrations at its sites of action. The desloratadine dose administered as well as the appropriate concentration attained at its sites of action are dependent upon the rate and extent of drug absorption, distribution; binding in tissues, biotransformation (metabolism) and excretion. The absorption, distribution, biotransformation and excretion of desloratadine all involve its transport across cell membranes.
Ideally, a drug should exhibit linear pharmacokinetics whereby the plasma concentrations of the drug plasma and the active drug metabolite(s), if any, increase in proportion to the drug dose. It is unpredictable which drugs will exhibit non-linear pharmacokinetics. This unpredictability may arise due to saturation of protein binding, hepatic metabolism or active renal transport of the drug and its active metabolite.
The molecular size, solubility at the site of absorption, degree of ionization and relative lipid solubility of the ionized and nonionized forms of a drug are important characteristics that affect the transport across cell membranes. These important characteristics are different for desloratadine (a secondary amine) and its active metabolite, 3-hydroxydesloratadine (a hydroxy-substituted secondary amine) and loratadine (a tertiary amine) so that transport across cell membranes and pharmacokinetics profiles may be different for each.
Drugs with non-linear pharmacoketics lack a proportional relationship between drug dose and drug plasma concentration which leads to burdensome physician and patient monitoring to achieve the targeted therapeutically effective plasma concentrations while avoiding significant periods of subtherapeutic or even toxic plasma levels.
There is a need for a clinically effective therapy for the use of desloratadine to treat or prevent such allergic and inflammatory conditions of the skin and airway passages in a human airway passages in a human.